ICON-2: FMT and Bezlotoxumab Compared to FMT and Placebo for Patients With IBD and CDI

Mass General Brigham

Status and phase: Completed; Phase 2

Conditions: Inflammatory Bowel Diseases; Clostridium Difficile Infection

Treatments: Drug: Fecal Microbiota Transplantation; Drug: Bezlotoxumab; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03829475

2018

Details and patient eligibility

About

This is a randomized controlled trial to assess the clinical and microbiological impacts of FMT in combination with Bezlotoxumab (bezlo) compared to FMT in combination with placebo in patients with both inflammatory bowel disease (IBD) a and clostridium difficile infection (CDI). The investigators will prospectively enroll up to 150 IBD-CDI patients from 4 tertiary care FMT referral centers. Patients will be randomized 1:1 to either receive FMT in combination with Bezlo of FMT and a placebo infusion. Donor stool from healthy donors will be obtained from OpenBiome. OpenBiome is a nonprofit 501(c)(3) organization that provides hospitals with screened, filtered, and frozen material ready for clinical use. Patients will be enrolled and followed prospectively for 3 months post therapy. Stool and blood samples as well as clinical data will be collected at baseline, week 1, 8 and 12.

Enrollment: 61 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults age 18 or greater
• History of ≥ 2 episodes of recurrent CDI. CDI is defined as the presence of diarrhea ( Bristol 6 or 7 for 48 hours and a confirmatory test for CDI). Preferred testing will be a two-step method using GDH/EIA toxin, though PCR will be accepted based on hospital availability with confirmation of the most recent episode occurring within the prior 3 months
• Confirmed diagnosis of IBD (ulcerative colitis, Crohn's disease or indeterminate colitis)
• Undergoing FMT via colonoscopy for CDI as part of standard medical care

Exclusion criteria

• Unable or unwilling to undergo a colonoscopy
• Inpatient status, though patients can be screened while inpatients, the must be outpatient for the planned colonoscopy.
• Anticipated immediate or upcoming surgery within 30 days
• Need for continued non-anti-CDI antibiotic therapy
• History of total proctocolectomy
• Female patients who are pregnant or breastfeeding or plan to become pregnant in the next 6 months.
• Patients who are unable to give informed consent
• Participation in a clinical trial in the preceding 30 days or simultaneously during this trial
• Severe food allergy (anaphylaxis or anaphylactoid-like reaction)
• Life expectancy < 6 months
• Unable to adhere to protocol requirements
• Patient who have received an FMT in the past year
• Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines that it will put the subject at greater risk from FMT
• Patient who is diagnosed with NYHA class 3 or 4 Heart Failure
• Lab value of WBC <3.0 x 103/mm3 , Platelets <100 x 103/mm3 , ALT or AST > 1.5 x institutional ULN
• EBV or CMV negative if a patient is severely immunosuppressed ( defined as 3 or more immunosuppressing agents)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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61 participants in 2 patient groups, including a placebo group

FMT + Bezlo

Experimental group

Description:

Patients in this arm will received an FMT via colonoscopy ( 250ml) as well as a single IV infusion of bezlotoxumab (10mg/kg) that will take place over 60 mins.

Treatment:

Drug: Bezlotoxumab

Drug: Fecal Microbiota Transplantation

FMT + Placebo

Placebo Comparator group

Description:

Patients in this arm will receive a single FMT via colonoscopy (250ml) and a placebo (saline) infusion (250cc) over

Treatment:

Drug: Placebo

Drug: Fecal Microbiota Transplantation